Trimipramine is a tricyclic antidepressant used in the therapy of major (endogenous) as well as reactive (exogenous) depression. In clinical trials, trimipramine therapy was not associated with an increased rate of elevations in serum aminotransferase levels, and it has yet to be linked to instances of clinically apparent acute liver injury.
Trimipramine is a tricyclic antidepressant (TCA) which is used to treat depression. It has also been used for its sedative, anxiolytic, and weak antipsychotic effects in the treatment of insomnia, anxiety disorders, and psychosis, respectively. The drug is described as an atypical or “second-generation” TCA because, unlike other TCAs, it seems to be a fairly weak monoamine reuptake inhibitor. Similarly to other TCAs however, trimipramine does have antihistamine, antiserotonergic, antiadrenergic, antidopaminergic, and anticholinergic activities.
Mechanism of action of Trimipramine
Trimipramine’s mechanism of action differs from other tricyclic antidepressants. Trimipramine acts by decreasing the reuptake of norepinephrine and serotonin (5-HT). It is now thought that changes occur in receptor sensitivity in the cerebral cortex and hippocampus. The hippocampus is part of the limbic system, a part of the brain involved in emotions. Presynaptic receptors are affected: a1 and b1 receptors are sensitized, a2 receptors are desensitized (leading to increased noradrenaline production). Tricyclics are also known as effective analgesics for different types of pain, especially neuropathic or neuralgic pain. A precise mechanism for their analgesic action is unknown, but it is thought that they modulate anti-pain opioid systems in the CNS via an indirect serotonergic route.
Indications of Trimipramine
- Depression
- Nocturnal Enuresis
- Sleeplessness
- Anxiety,
- Agitation
- Panic Disorder
- Sleep Paralysis
- Trichotillomania
- Diabetic neuropathies
- Migraines
- Sleep disorders and disturbances
- Body dysmorphic disorder
- Premature ejaculation
- Depersonalization disorder
- For the treatment of depression and depression accompanied by anxiety, agitation or sleep disturbance
Contra-Indications of Trimipramine
- Overactive thyroid gland
- Decreased blood Platelets
- Decreased neutrophils a type of white blood cell
- Schizophrenia
- Behaving with excessive cheerfulness and activity
- A mild degree of mania
- Manic-depression
- Having thoughts of suicide
- Alcoholism
- Serotonin syndrome – adverse drug interaction
- Closed-angle glaucoma
- Heart attack within the last 30 days
- Coronary artery disease
- Prolonged QT interval on EKG
- Abnormal heart rhythm
- Disease of the heart and blood vessels
- Abnormal EKG with QT changes from birth
- Stroke
- Liver problems
- Kidney disease with a reduction in kidney function
- Enlarged prostate
Dosage of Trimipramine
Strengths: 25 mg; 50 mg; 100 mg
Depression
Outpatients/Office Patients
- Initial dose: 75 mg orally per day in divided doses
- Maintenance dose: 50 to 150 mg orally per day
- Maximum dose: 200 mg/day
Hospitalized patients
- Initial dose: 100 mg orally per day in divided doses
- Maintenance dose: 200 mg orally per day
- Maximum dose: 300 mg/day
Side Effects of Trimipramine
The most common
- Constipation
- dizziness
- drowsiness
- dry mouth
- chest pain
- headache
- joint painPain
- dizziness
- nausea and vomiting
- Severe stomach ache
- epigastric pain,
- diarrhoea,
- anorexia,
- flatulence,
- headache,
- fainting, fast or pounding heartbeats.
More common
- Seizures
- Syndrome of inappropriate secretion of antidiuretic hormone
- Fast or irregular heartbeat
- fever
- Back pain
- dizziness
- headache
- increased cough
- Acid or sour stomach
- decreased appetite
- Agitation
- chest congestion
- chest pain
- confusion
- decreased sexual ability or desire
- diarrhea or loose stools
- heartburn
- sleepiness or unusual drowsiness
- stomach or abdominal cramps, gas, or pain
- trouble sleeping
Less common
- Abnormal dreams
- change in sense of taste
- congestion
- discouragement, feeling sad, or empty
- Suicide attempts
- Acting on dangerous impulses
- Aggressive or violent behavior
- Thoughts about suicide or dying
- New or worse depression
- New or worse anxiety or panic attacks
- Agitation, restlessness, anger, or irritability
- Trouble sleeping
- An increase in activity or talking more than normal
Drug Interactions of Trimipramine
Trimipramine may interact with following drugs, supplements & may decrease the efficacy of the drug
- alcohol
- alpha blockers (e.g., alfuzosin, doxazosin, silodosin, tamsulosin)
- amphetamines (e.g., dextroamphetamine, lisdexamphetamine)
- antihistamines (e.g., cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
- antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- baclofen
- barbiturates (e.g., butalbital, pentobarbital phenobarbital)
- benzodiazepines (e.g., chlordiazepoxide, clonazepam, diazepam, lorazepam)
- beta-adrenergic blockers (e.g., atenolol, propranolol, sotalol)
- bupropion
- calcitriol
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- carvedilol
- ciprofloxacin
- clobazam
- oral corticosteroids (e.g., dexamethasone, hydrocortisone, prednisone)
- cyclosporine
- doxycycline
- estrogens (e.g., conjugated estrogen, estradiol, ethinyl estradiol)
- folic acid
- gabapentin
- “gliptin” diabetes medications (e.g., linagliptin, saxagliptin, sitagliptin)
- lansoprazole
- loperamide
- losartan
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- methylphenidate
- montelukast
- ondansetron
- phenytoin
- progestins (e.g., dienogest, levonorgestrel, medroxyprogesterone, norethindrone)
- proton pump inhibitors (e.g., lansoprazole, omeprazole)
- ranitidine
- selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, duloxetine, fluoxetine, paroxetine, sertraline)
- sildenafil
- “statin” anti-cholesterol medications (e.g., atorvastatin, lovastatin, simvastatin)
- theophyllines (e.g., aminophylline, oxtriphylline, theophylline)
- thiazide diuretics (e.g., chlorothiazide, hydrochlorothiazide)
- tramadol
- tricyclic antidepressants (e.g., amitriptyline, desipramine, )
- warfarin
Pregnancy & Lactation of Trimipramine
FDA Pregnancy Category C
Pregnancy
The safety of trimipramine for use during pregnancy has not been established. If you are or may be pregnant, the possible benefits of taking this medication must be weighed against the possible risks. If you are or may be pregnant, talk to your doctor.
Lactation
The safety of trimipramine for use while breastfeeding has not been established. If you are breastfeeding, the possible benefits of taking this medication must be weighed against the possible risks to the child. If you are breastfeeding, talk to your doctor.
References
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